Neurodegenerative disorders and brain health are among the major emerging public health challenges facing our aging society. Alzheimer's disease (AD) is by far the most prevalent of the neurodegenerative disorders. Several aging pathologies, such as Parkinson's disease, Huntington's disease and ALS, are known to share some pathophysiology with Alzheimer's disease, including aberrant protein folding and oxidative stress. Sayre, L. M., G. Perry, et al. (2008). “Oxidative stress and neurotoxicity.” Chem Res Toxicol 21(1): 172-88.
In addition to selective neuronal degeneration, AD is characterized pathologically by the presence of two hallmark lesions in the brain: extracellular senile plaques (SP) and intraneuronal neurofibrillary tangles (NFT). SP contain amyloid-β (Aβ) peptides, primarily Aβ(1-42); whereas, NFT are composed mainly of the microtubule-associated protein Tau in the form of paired helical filaments. The pathophysiology of AD is also characterized by increased production of soluble peptides of Amyloid Beta—peptides Aβ(1-40) and Aβ(1-42). Some recent findings suggest that neuronal toxicity and compromised synaptic transmission may be due to increased production of soluble oligomers of Aβ.
A need exists for compounds and compositions that treat neurodegenerative disorders and/or improve brain health. Ideally, such compounds would have good pharmaceutical properties, such as solubility, bioavailability and/or few side effects.